The overall objective is to further elucidate the biological mode of action of N-nitrosamines by: 1) Testing unusual model N-nitrosamines (alpha-, beta-substituted, etc.) in vivo for carcinogenicity and in vitro for mutagenicity and oncogenic transformation. 2) Determining potential of nuclear enzymes in intact isolated nuclei to activate 14C-nitrosamines which then bind to nuclear DNA. 3) Determining potential of purified microsomal enzymes (cytochrome P-450, etc.) to activate nitrosamines. 4) Determining effect (in terms of metabolism) of specifically deuterated alpha, beta and delta positions to purified and unpurified microsomal enzymes.